Small-cell lung cancer (SCLC) combined with epidermal growth factor receptor (EGFR) mutations is extremely rare, and standard chemotherapeutic strategies have not yet been established. In the present study, we report a case of a 67-year-old man who presented with combined SCLC with EGFR mutation (exon 19 deletion). Systemic chemotherapy with cisplatin and irinotecan was initiated as first-line chemotherapy, and computed tomography findings revealed tumor shrinkage after two cycles of chemotherapy. However, after the third cycle of the treatment, disease progression was observed including the appearance of pleural and pericardial effusion...

Introduction: Tyrosine kinase inhibition of the epidermal growth factor receptor (EGFR) is the standard in the first line treatment of patients with advanced non-small-cell lung cancer (NSCLC) harbouring EGFR activating mutations. Here we aim to discern efficacy and toxicity measures through a meta-analysis of published studies that could aid treatment selection. Materials And Methods: We performed a meta-analysis of the main randomized clinical trials evaluating the currently approved EGFR-TKIs in first-line of treatment of EGFR-positive advanced NSCLC...

Human epidermal growth factor receptor 2 (HER2) plays an important role in the pathogenesis of various cancers. HER2 alterations have been suggested to be a therapeutic target in non-small-cell lung cancer (NSCLC), just as in breast and gastric cancers. We previously reported that the pan-HER inhibitor afatinib could be a useful therapeutic agent as HER2-targeted therapy for patients with NSCLC harboring HER2 alterations. However, acquired resistance to afatinib was observed in the clinical setting, similar to the case for other HER inhibitors...

We report a case of pleomorphic carcinoma with exon 18 mutation (G719X) of the epidermal growth factor receptor (EGFR), which showed good response to afatinib and resulted in successful resection. To our knowledge, this is the first report on the use of afatinib for pleomorphic carcinoma followed by the surgical resection. The patient was a 59-year-old woman, who visited our hospital because chest computed tomography showed a 28 × 28-mm nodule in the left upper lobe. Bronchoscopy was performed and the histological findings of transbronchial biopsy revealed adenosquamous carcinoma positive for G719X mutation in exon 18 of the EGFR...

The present study investigated the toxicity of HangAmDan-B1 (HAD-B1) on A549-Cisplatin resistant (A549CR) cells. HAD‑B1 inhibited the growth of A549CR cells in a concentration‑dependent manner; HAD‑B1 was more effective at inhibiting A549CR cell viability compared with vehicle‑treated cells. The reduction in viability may be due to S‑phase cell cycle arrest and the induction of apoptosis in HAD‑B1‑treated cells. Cell cycle protein profile analysis of HAD‑B1‑treated A549CR cells using an InnoPharmaScreen (IPS) ProteoChip‑based antibody microarray chip indicated downregulation of signal transducer and activator of transcription 3...

Non-small cell lung cancers (NSCLC) harboring the uncommon epidermal growth factor receptor (EGFR) exon 20 insertion mutations are generally thought to be unresponsive to EGFR-tyrosine kinase inhibitor (TKI) therapy. Presented here is a case of stage IV NSCLC harboring an uncommon EGFR exon 20 insertion mutation that was maintained at minimal progressive disease for 54 months, with 36 months on the second-generation TKI afatinib. Contrary to the existing literature, the patient in this case demonstrated a long, durable response to the EGFR-TKI, which was exhibited by a long survival endpoint...

A 65-year-old female with diabetes mellitus but otherwise good health in the past suffered from cough with occasional blood-stained sputum during initial presentation. The patient was diagnosed with pulmonary poorly differentiated adenocarcinoma with an epidermal growth factor receptor (EGFR) exon 19 deletion and hence received afatinib therapy for 25 months without obvious adverse events except for a grade 1-2 acneiform rash. The disease was stabilized after subsequent cycles of chemotherapy with pemetrexed and carboplatin followed by maintenance pemetrexed...

Targeting ErbB family of receptors is an important therapeutic option, because of its essential role in the broad spectrum of human cancers, including non-small cell lung cancer (NSCLC). Therefore, in the present work, considerable effort has been made to develop an inhibitor against HER family proteins, by combining the use of pharmacophore modelling, docking scoring functions, and ADME property analysis. Initially, a five-point pharmacophore model was developed using known HER family inhibitors. The generated model was then used as a query to screen a total of 468,880 compounds of three databases namely ZINC, ASINEX, and DrugBank...

BACKGROUND/AIM: Although afatinib has a strong efficacy, it can be toxic; hence, we aimed to determine markers of response to afatinib in order to assess prognosis. PATIENTS AND METHODS: Information on clinical background, therapeutic effects, and adverse events was collected retrospectively at one Institution from patients treated with afatinib as initial epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI). We examined the relationship between different adverse events and their effects on prognosis...

BACKGROUND: Brain metastases (BM) are frequent in non-small cell lung cancer (NSCLC) patients, but there is a lack of evidence-based management of this patient group. We aimed to capture a snapshot of routine BM management in Europe to identify relevant research questions for future clinical trials. METHODS: An EORTC Lung Cancer Group (LCG) online survey containing questions on NSCLC BM screening and treatment was distributed between 16/02/17 and 15/06/17 to worldwide EORTC LCG members, and through several European scientific societies in the thoracic oncology field...

BACKGROUND: Afatinib is an irreversible multi-targeted TKI, used in the treatment with EGFR mutated non-small cell lung cancer (NSCLC). The purpose of this study is to explore the molecular pharmacokinetic mechanism underlying the effect of P-gp inhibitors on the intestinal absorption and biliary excretion and to understand how P-gp inhibitors affect afatinib pharmacokinetics. METHODS: Pharmacokinetics in vivo, in situ intestinal perfusion, perfused rat liver in situ, Caco-2 cells, P-gp ATPase activity, sandwich-cultured rat hepatocytes (SCRH) and transfected-cell transport were used in the evaluation...

Molecularly targeted therapy has enabled outstanding advances in cancer treatment. Whereas various anti-HER2 drugs have been developed, trastuzumab is still the only anti-HER2 drug presently available for gastric cancer. In this study, we propose novel treatment options for patients with HER2-positive gastric cancer. At first, we determined the molecular profiles of 12 gastric cancer cell lines, and examined the antitumor effect of the pan-HER inhibitors afatinib and neratinib in those cell lines. Additionally, we analyzed HER2 alteration in 123 primary gastric cancers resected from Japanese patients to clarify possible candidates with the potential to respond to these drugs...

Patients with non-small-cell lung cancer (NSCLC) whose tumours harbour activating mutations within the epidermal growth factor receptor (EGFR) frequently derive significant clinical and radiographic benefits from treatment with EGFR tyrosine kinase inhibitors (TKIs). As such, prospective identification of EGFR mutations is now the standard of care worldwide. However, acquired therapeutic resistance to these agents invariably develops. Over the past 10 years, great strides have been made in defining the molecular mechanisms of EGFR TKI resistance in an effort to design rational strategies to overcome this acquired drug resistance...

BACKGROUND: The process of selecting patients on the basis of epidermal growth factor receptor (EGFR) mutations would likely result in a patient population with greater sensitivity to EGFR tyrosine kinase inhibitors (EGFR-TKIs). However, EGFR mutation status is not routinely examined in patients with squamous cell lung cancer (Sq) because of the low incidence of EGFR mutations and the poor clinical response to EGFR-TKIs. METHODS: We retrospectively reviewed the clinical features of patients at our hospital with Sq who carried EGFR-TKI-sensitive EGFR mutations and assessed their responses to EGFR-TKIs...

Background: Three different tyrosine kinase inhibitors have been approved as first-line therapies for epidermal growth factor receptor (EGFR) mutation-positive advanced non-small-cell lung cancer with similar overall survival. This study determined dynamic changes in quality of life (QoL) for patients using these therapies after controlling for potential confounders. Methods: From 2011 to 2016, we prospectively assessed the utility values and QoL scores of patients using the EuroQol five-dimension and World Health Organization Quality-of-Life - Brief questionnaires...